Despite the continued efforts, a batch-insensitive tool that can both infer and predict the developmental dynamics using single-cell genomics is lacking. Here, I present scTour, a novel deep learning ...architecture to perform robust inference and accurate prediction of cellular dynamics with minimal influence from batch effects. For inference, scTour simultaneously estimates the developmental pseudotime, delineates the vector field, and maps the transcriptomic latent space under a single, integrated framework. For prediction, scTour precisely reconstructs the underlying dynamics of unseen cellular states or a new independent dataset. scTour's functionalities are demonstrated in a variety of biological processes from 19 datasets.
This article reviews the current state of knowledge regarding the epidemiology of frailty by focusing on 6 specific areas: (1) clinical definitions of frailty, (2) evidence of frailty as a medical ...syndrome, (3) prevalence and incidence of frailty by age, gender, race, and ethnicity, (4) transitions between discrete frailty states, (5) natural history of manifestations of frailty criteria, and (6) behavior modifications as precursors to the development of clinical frailty.
The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional views on cell identity and cell fate ...determination. Direct reprogramming (also known as transdifferentiation) refers to cell fate conversion without transitioning through an intermediary pluripotent state. Given that the number of cell types that can be generated by direct reprogramming is rapidly increasing, it has become a promising strategy to produce functional cells for therapeutic purposes. This Review discusses the evolution of direct reprogramming from a transcription factor-based method to a small-molecule-driven approach, the recent progress in enhancing reprogrammed cell maturation, and the challenges associated with in vivo direct reprogramming for translational applications. It also describes our current understanding of the molecular mechanisms underlying direct reprogramming, including the role of transcription factors, epigenetic modifications, non-coding RNAs, and the function of metabolic reprogramming, and highlights novel insights gained from single-cell omics studies.
Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some ...biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
A transition‐metal‐free visible‐light‐promoted radical phosphorylation/cyclization of N‐allylbenzamides with phosphine oxides for the synthesis of phosphoryl‐substituted dihydroisoquinolones was ...developed under room temperature. This protocol features mild reaction conditions, simple operation, broad substrate scope as well as scale‐up ability.
Analysis of the hydrogenation and dehydrogenation behaviors by kinetic models is an efficient approach to the in-depth understanding of the kinetic mechanism for hydrogen storage materials. A large ...number of kinetic models as well as analysis methods based on these models have been extensively applied in hydrogen storage materials, and kinetic parameters with physical interpretations are determined to reveal the kinetic mechanism of hydrogenation and dehydrogenation reactions. However, the assumptions and derivation steps of these models are usually difficult to find, and the selection of analysis methods is sometimes confusing. Moreover, some recently proposed models and analysis methods have not been introduced to investigate the kinetic mechanism of hydrogen storage materials yet. These problems significantly prevent the kinetic models as well as analysis methods from further revealing the kinetic mechanism for hydrogen storage materials. Therefore, this review mainly focuses on the illustration of the assumptions and derivation steps of the kinetic models, summarization of corresponding analysis methods, and introduction of some recently proposed kinetic models and analysis methods for hydrogen storage materials.
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•Analysis of kinetic behaviors for hydrogen storage materials reveals mechanisms.•The assumptions and derivation steps of the kinetic models are illustrated.•The analysis methods on the basis of the kinetic models are summarized.•Some new proposed models and analysis methods are introduced.
While the f0 realization of lexical tones vary extensively in contexts, little has been known on how listeners process the variation in lexical tones due to contextual effects such as tonal ...coarticulation in spoken word recognition. This study thus aims to fill the knowledge gap in tone perception with evidence from two types of anticipatory tonal coarticulation effects in Tianjin Mandarin, i.e., the slope raising effect due to a following low-falling tone and the overall-height raising effect due to a following low-dipping tone. An eye-tracking experiment with the Visual World Paradigm was carried out to compare participants' eye movements when they heard targets in three types of anticipatory raising conditions, i.e., the Slope Raising condition, the Overall-height Raising condition, as well as the No Raising condition (the baseline). The eye movement results showed significant differences in the proportion of looks to target between the Slope Raising condition versus the other two conditions, whereas the Overall-height Raising condition did not differ significantly from the No Raising condition. The findings thus suggest the facilitatory effect of tonal coarticulation cues in the anticipation of the upcoming tones, but listeners in this study seemed to be only sensitive to the raising in the f0 slope rather than the overall raising in the f0 height.
Environment‐friendly lead‐free piezoelectric ceramics have been studied extensively in the past decade with great progress particularly in systems based on a niobate perovskite compound formulated as ...(K, Na)NbO3 (abbreviated as KNN). A comprehensive review on the latest development of KNN‐based piezoelectric ceramics is presented in this article, including the phase structure, property enhancement approaches, and sintering processes as well as the status of some promising applications. The phase structure of KNN was reexamined and associated with the effect of chemical modification on its tetragonal‐to‐orthorhombic transition. Then, a special focus is placed on the temperature dependence of piezoelectric properties of KNN‐based ceramics, followed by reviewing the recent approaches devoted to the temperature‐stability enhancement. The processing fundamentals related to the sintering of KNN‐based ceramics are also presented with an emphasis on compositional and microstructural control. Finally, this review introduces several industrial attempts of traditional piezoceramic products using KNN‐based ceramics and the studies on some promising application in authors' laboratory.
Frailty is recognized as a cornerstone of geriatric medicine. It increases the risk of geriatric syndromes and adverse health outcomes in older and vulnerable populations. Although multiple screening ...instruments have been developed and validated to improve feasibility in clinical practice, frequent lack of agreement between frailty instruments has slowed broad implementation of these tools. Despite this, interventions to improve frailty-related health outcomes developed to date include exercise, nutrition, multicomponent interventions, and individually tailored geriatric care models. Possible strategies to prevent frailty include lifestyle or behavioral interventions, proper nutrition, and increased activity levels and social engagement.
Current international guidelines recommend aerobic, resistance, and combined exercises for the management of type 2 diabetes mellitus (T2DM). In our study, we conducted a network meta-analysis to ...assess the comparative impact of different exercise training modalities on glycemic control, cardiovascular risk factors, and weight loss in patients with T2DM.
We searched five electronic databases to identify randomized controlled trials (RCTs) that compared the differences between different exercise training modalities for patients with T2DM. The risk of bias in the included RCTs was evaluated according to the Cochrane tool. Network meta-analysis was performed to calculate mean difference the ratio of the mean and absolute risk differences. Data were analyzed using R-3.4.0.
A total of 37 studies with 2208 patients with T2DM were included in our study. Both supervised aerobic and supervised resistance exercises showed a significant reduction in HbA1c compared to no exercise (0.30% lower, 0.30% lower, respectively), however, there was a less reduction when compared to combined exercise (0.17% higher, 0.23% higher). Supervised aerobic also presented more significant improvement than no exercise in fasting plasma glucose (9.38 mg/dl lower), total cholesterol (20.24 mg/dl lower), triacylglycerol (19.34 mg/dl lower), and low-density lipoprotein cholesterol (11.88 mg/dl lower). Supervised resistance showed more benefit than no exercise in improving systolic blood pressure (3.90 mmHg lower) and total cholesterol (22.08 mg/dl lower. In addition, supervised aerobic exercise was more powerful in improving HbA1c and weight loss than unsupervised aerobic (HbA1c: 0.60% lower; weight loss: 5.02 kg lower) and unsupervised resistance (HbA1c: 0.53% lower) exercises.
Compared with either supervised aerobic or supervised resistance exercise alone, combined exercise showed more pronounced improvement in HbA1c levels; however, there was a less marked improvement in some cardiovascular risk factors. In terms of weight loss, there were no significant differences among the combined, supervised aerobic, and supervised resistance exercises.
Our study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42017067518 .
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